PROJECT SUMMARY We seek funds to purchase a Promethion Core System for mice (Promethion) from Sable Systems International. The requested instrument consists of 16 mouse home cages connected to sensors that measure oxygen consumption and carbon dioxide production. These measurements are used to estimate energy expenditure and substrate oxidation. Furthermore, the Promethion has the capacity to measure real-time food intake, water intake, locomotor activity and body weight. Cages are placed inside a temperature controlled cabinet that allows for experiments to be performed at different ambient temperatures (4-50C). In addition to these features, three new accessories are being requested for this instrument. First, a stable isotope gas analyzer is requested for the measurement of 13C and 18O in exhaled breath for precise assessments of substrate oxidation from either exogenously- or endogenously-labeled sources. Second, metabolic cages designed for use with optogenetics systems are being requested in order to measure the effect of modulating brain circuits/neurons on energy balance parameters. Lastly, motorized treadmills are requested that can interface with the Promethion to assess various parameters of energy expenditure and substrate oxidation during forced exercise. Altogether, these capabilities will satisfy existing NIH projects at Vanderbilt University and Vanderbilt University Medical Center as well as the growing demand for these services from external academic institutions and for-profit client institutions. These analyses are of particular relevance to investigators focusing on metabolic diseases such as diabetes and obesity. However, the instrument can also be used to assess metabolic phenotypes in mouse models of other diseases such as inflammatory disease and cancer. The Promethion will be incorporated into the Vanderbilt Mouse Metabolic Phenotyping Center (MMPC). For twenty years, the MMPC has provided the scientific community with metabolic phenotyping services for mouse models of metabolic diseases including assessments of energy balance phenotypes. Our current energy balance instrument (a 16 cage Promethion system) is old (10 years) and is used beyond its designed capacity. This leads to long wait times and reduced productivity for researchers. The acquisition of a new system will not only address the need for a redundant system but will also reduce wait times and significantly improve scientific productivity. Furthermore, the new capabilities described above will allow the MMPC to expand to a user base that was previously not using this instrument. Vanderbilt University is providing space and financial support for the successful operation of this instrument.